Transplantation is the treatment of choice for many patients with organ failure such as end-stage renal, hepatic or pulmonary disease, refractory heart failure, and various other conditions. Despite a considerable advancement in therapeutic modalities, allograft rejection continues to pose a serious threat to the overall survival of transplant patients. Chronic rejection remains the most important cause of graft loss with a prevalence rate as high as 80% in some renal transplantation series, thus limiting the overall success of solid organ transplantation. The mechanisms that prevent permanent allograft acceptance are uncertain and have not been systematically investigated. For these reasons, current clinical strategies are focused primarily on prevention and early diagnosis since there are no effective therapies that permanently safeguard the allograft against rejection in the absence of continuous, potentially harmful, immunosuppression.
Currently, chronic rejection of transplanted organs is diagnosed by pathological analysis, which requires a biopsy of the allograft. This procedure is invasive by nature with potential complications such as bleeding, infection or organ perforation. It is a costly multidisciplinary procedure involving surgeons, anesthesiologists, Operating Room personnel, histotechnologists and pathologists. It is subject to sampling error and the diagnosis may be overlooked or misinterpreted by the examining pathologist due to very subtle or non-specific pathological changes as described in the literature. Indeed, the pathological criteria used to establish the diagnosis of chronic rejection including thickening of intimal layer with luminal narrowing and fibrosis of the interstitium are non-specific findings that may be seen in other diseases or conditions such as diabetes, hypertension or aging, which may lead to false positive results. In addition, these changes can be very minimal and focal in nature so that they may be overlooked and completely missed, thus reducing the sensitivity of this technique particularly in early detection. These overall limitations are due to the absence of a specific diagnostic marker of chronic rejection. Therefore, there is a continuing need in the field of organ transplantation to identify markers that can be used for the accurate and early diagnosis of chronic allograft rejection.